LRP1 and Alzheimer disease: Researchers also observed that the APOE4 isoform is a major risk factor for AD, and that the binding of Aβ with apoE4 shifts fast clearance of soluble Aβ40/42 from LRP1 to VLDLR; hence, Aβ-apoE4 complexes at the BBB are cleared with a slower rate than LRP1 (Deane et al., 2008; Tachibana et al., 2019).